Mechanism of Tissue Damage (Pathogenesis)
Normally, immune complexes are cleared by the body, but in the setting of antigen excess or complement deficiency, their clearance is impaired. As a result, soluble complexes deposit in vessel walls, basement membranes, and structures bearing Fc receptors.
The inflammatory cascade develops in sequential stages:
- Cellular Activation. Platelets and basophils are immediately involved in the process.
- Mediator Release. These cells release pro-inflammatory cytokines (including TNF-α), chemokines, and vasoactive amines (primarily histamine), which dramatically increase vascular permeability.
- Vascular Abnormalities. Platelet aggregation occurs, leading to the formation of multiple microthrombi in capillaries.
- Cellular Infiltration and Necrosis. Complement components (anaphylatoxins C3a, C4a, C5a) act as chemoattractants. Driven by C5a, neutrophils rush to the site. They release aggressive lysosomal enzymes that directly destroy tissue and cause necrosis.
- Late Stage. In the final stages of inflammation, macrophages join the process.
Classification and Clinical Manifestations
Triggers of inflammation can be either exogenous antigens (pathogens of chronic bacterial, viral, fungal, and protozoal infections) or endogenous autoantigens.
Systemic Forms Characterized by the circulation of immune complexes throughout the body. Their deposition causes systemic vasculitis, arthritis (joints), and nephritis (kidneys). A classic example is serum sickness. It occurs following the administration of large doses of a foreign protein, such as therapeutic equine anti-tetanus serum. The pathology has a latent period of 6–7 days—the time required for the immune system to generate a sufficient antibody titer.
Organ-Specific (Localized) Forms The reaction localizes to a specific tissue. In systemic lupus erythematosus (SLE), the skin is affected, while lupus nephritis targets the kidneys. An important clinical phenomenon is the Arthus reaction. It develops upon repeated intradermal injection of an antigen due to the local formation of complexes with preexisting antibodies. 3 to 10 hours after injection, pronounced edema, hemorrhagic inflammation, and tissue necrosis appear at the injection site.
Laboratory Diagnostics
To confirm Type III hypersensitivity, immune deposits must be visualized or their concentration in the bloodstream evaluated:
- Tissue Analysis (Biopsies). The gold standard is the direct immunofluorescence (IF) assay. This method detects specific fluorescence of immunoglobulin and complement component deposits directly within the affected structures.
- Blood Analysis. Precipitation of circulating immune complexes using polyethylene glycol is utilized. After precipitation, the concentration of IgG in the resulting pellet is measured.